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      Cardiovascular Disease Management With Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Type 2 Diabetes: A Cardiology Primer

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          Abstract

          Patients with type 2 diabetes face an elevated risk of cardiovascular disease. This review centers on sodium-glucose cotransporter-2 (SGLT2) inhibitors, a class of drugs that, according to a growing body of evidence, may have major potential for managing cardiovascular disease in patients with type 2 diabetes. This review presents findings from multiple clinical trials suggesting that SGLT2 inhibitors can not only serve as preventive therapeutic agents but also play a role in the active management of heart failure. The discussion includes the mechanism of action of SGLT2 inhibitors, emphasizing that they enhance urinary glucose excretion, which could lead to improved glycemic control and contribute to metabolic shifts beneficial to cardiac function. Alongside these cardiometabolic effects, safety concerns and practical considerations for prescribing these agents are addressed, taking into account potential adverse effects such as genitourinary infections and diabetic ketoacidosis as well as the financial implications for patients. Despite these drawbacks, therapeutic indications for SGLT2 inhibitors continue to expand, including for kidney protection, although further research is necessary to fully understand the mechanisms driving the cardioprotective and kidney-protective effects of SGLT2 inhibitors. By synthesizing current knowledge, this review intends to inform and guide clinical decision-making, thereby enhancing cardiovascular disease outcomes in patients with type 2 diabetes.

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          Most cited references50

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          Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes.

          The effects of empagliflozin, an inhibitor of sodium-glucose cotransporter 2, in addition to standard care, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk are not known.
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            Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction

            In patients with type 2 diabetes, inhibitors of sodium-glucose cotransporter 2 (SGLT2) reduce the risk of a first hospitalization for heart failure, possibly through glucose-independent mechanisms. More data are needed regarding the effects of SGLT2 inhibitors in patients with established heart failure and a reduced ejection fraction, regardless of the presence or absence of type 2 diabetes.
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              Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes

              Background Canagliflozin is a sodium-glucose cotransporter 2 inhibitor that reduces glycemia as well as blood pressure, body weight, and albuminuria in people with diabetes. We report the effects of treatment with canagliflozin on cardiovascular, renal, and safety outcomes. Methods The CANVAS Program integrated data from two trials involving a total of 10,142 participants with type 2 diabetes and high cardiovascular risk. Participants in each trial were randomly assigned to receive canagliflozin or placebo and were followed for a mean of 188.2 weeks. The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Results The mean age of the participants was 63.3 years, 35.8% were women, the mean duration of diabetes was 13.5 years, and 65.6% had a history of cardiovascular disease. The rate of the primary outcome was lower with canagliflozin than with placebo (occurring in 26.9 vs. 31.5 participants per 1000 patient-years; hazard ratio, 0.86; 95% confidence interval [CI], 0.75 to 0.97; P<0.001 for noninferiority; P=0.02 for superiority). Although on the basis of the prespecified hypothesis testing sequence the renal outcomes are not viewed as statistically significant, the results showed a possible benefit of canagliflozin with respect to the progression of albuminuria (hazard ratio, 0.73; 95% CI, 0.67 to 0.79) and the composite outcome of a sustained 40% reduction in the estimated glomerular filtration rate, the need for renal-replacement therapy, or death from renal causes (hazard ratio, 0.60; 95% CI, 0.47 to 0.77). Adverse reactions were consistent with the previously reported risks associated with canagliflozin except for an increased risk of amputation (6.3 vs. 3.4 participants per 1000 patient-years; hazard ratio, 1.97; 95% CI, 1.41 to 2.75); amputations were primarily at the level of the toe or metatarsal. Conclusions In two trials involving patients with type 2 diabetes and an elevated risk of cardiovascular disease, patients treated with canagliflozin had a lower risk of cardiovascular events than those who received placebo but a greater risk of amputation, primarily at the level of the toe or metatarsal. (Funded by Janssen Research and Development; CANVAS and CANVAS-R ClinicalTrials.gov numbers, NCT01032629 and NCT01989754 , respectively.).
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                Author and article information

                Journal
                Tex Heart Inst J
                Tex Heart Inst J
                thij
                The Texas Heart Institute Journal
                Texas Heart® Institute, Houston
                0730-2347
                1526-6702
                Jan-Jun 2024
                9 April 2024
                : 51
                : 1
                : e238375
                Affiliations
                [1 ]Department of Medicine, Baylor College of Medicine, Houston, Texas
                [2 ]Department of Cardiology, The Texas Heart Institute, Houston, Texas
                [3 ]Aga Khan University, Karachi, Pakistan
                [4 ]Department of Cardiology, Houston Methodist DeBakey Heart and Vascular Center, Houston, Texas
                Author notes
                Corresponding author: Matthew W. Segar, MD, MS, 6770 Bertner Ave, Houston, TX 77030 ( msegar@ 123456texasheart.org )

                Author Contributions: All authors made substantial contributions to the conception and design of the work; the acquisition, analysis, and interpretation of data for the work; and the drafting and critical revision of the work for important intellectual content. All authors gave final approval of the version to be published and agree to be held accountable for all aspects of the work to ensure that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

                Article
                10.14503/THIJ-23-8375
                11075510
                38590152
                404bf723-192c-4ccb-9849-2b61668d0a63
                © 2024 The Authors. Published by The Texas Heart Institute ®

                This is an Open Access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use and distribution in any medium, provided the original work is properly cited, and the use is noncommercial.

                History
                Page count
                Pages: 10
                Categories
                Narrative Review

                diabetes mellitus,cardiovascular diseases,hypoglycemic agents,sodium-glucose transporter 2 inhibitors,glycemic control,heart failure,atherosclerosis

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